The developing nervous system undergoes major shifts in neuron number during the period of synaptogenesis. The target tissue appears to have a major influence on the final number of neurons innervating the target region itself. While the mechanism underlying this interaction is not resolved, one strong hypothesis postulates the existence of trophic factors produced in the target region and retrogradely transported back to the projecting neuron. Deprivation of this trophic factor leads to neuron death. The biology of neural trophic factors has been best established in the peripheral nervous system, but has also been extensively investigated in the central nervous system of developing animals and, very recently, in the adult central nervous system. Fetal neural tissue may have significant quantities of trophic substances that might affect adult neuron death. This proposal seeks to define the effects of fetal neural tissue grafts on adult rats using a model of axotomy induced neuron death in the medial forebrain region. Specifically, the temporal and regional parameters of fetal grafts that are important in preventing cholinergic and GABAergic host neuron loss will be investigated. Furthermore, the importance of long term graft survival on host medial forebrain neurons will be assessed. Finally, the cellular components of the graft will be separated to quantify the individual effects of donor glia and donor neurons on host neuron death. By refining the parameters of the graft's effect on the host, it is hoped that the mechanisms underlying axotomy induced neuron death can be studied from a different perspective. The impact this research plan has on health care is derived from recent better understanding of neural events in chronic degenerative neurological disorders such as Parkinson's disease, Huntington's chorea and Alzheimer's disease. Loss of specific neuron populations in those diseases may be linked to loss of trophic substances. Furthermore, degree of recovery from acute neurologic diseases such as head trauma may be based on the extent of delayed neuron death can lead to manipulation of those mechanisms and improve outcome in a wide range of neurologic diseases.